P1381: EARLY FULL DONOR CHIMERISM AFTER FLAMSA RIC BASED ALLOGENEIC HSCT BUT NOT PRESENCE OF MORPHOLOGICAL REMISSION ASSOCIATES WITH OUTCOMES IN R/R AML PATIENTS
Authors: J. Ussmann, S. Hell, B. Schetschorke, G. Friedrich, C. Pfrepper, S. Schwind, M. Jentzsch, V. Vucinic, M. Herling, U. Platzbecker, G.-N. Franke
Journal: HemaSphere (2022)

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is still the only potentially curative treatment for patients (pts) with high-risk acute myeloid leukemia (AML). Despite recent advances, a significant number of pts are primary refractory or have early relapse (r/r) with <6 months (m) remission duration. One strategy to improve the outcomes of r/r AML is to perform HSCT after aplasia-inducing chemotherapy. Here, we report on a series of pts receiving a sequential chemotherapy regimen (fludarabine 30 mg/m2, amsacrine 100 mg/m2, cytarabine 2 g/m2 (FLAMSA)) and reduced-intensity conditioning (RIC) followed by HSCT as well as prophylactic donor lymphocyte infusions (DLI) as described by Schmid et al (JCO 2005). Aims: We aimed to retrospectively analyze the outcome of 82 consecutive pts with r/r AML who underwent FLAMSA RIC based HSCT between 2006 and 2020 at our center. Methods: Median age of the 82 pts was 55 years (y) and 38 pts (46%) were male. ELN risk and revised MRC prognostic classification at diagnosis were favorable in 8% and 4%, intermediate in 28% and 56%, and adverse in 64% and 40% of the pts, respectively. Median time from diagnosis to HSCT was 5 months. At the time of HSCT, only 3 pts (3%) were in complete remission (CR). RIC following the FLAMSA chemotherapy was 4Gy TBI and cyclophosphamide (73%), busulfan and cyclophosphamide (11%), melphalan (13%) or 2Gy TBI only (2%). 95% of pts received peripheral blood stem cells and 5% bone marrow (BM) from a matched unrelated donor (MUD, 63%), matched sibling donor (MSD, 10%), mismatch unrelated donor (MMUD, 23%) or a haploidentical donor (4%). Immunosuppression (IS) consisted of cyclosporine A, mycophenolate mofetil and antithymocyte globuline (MUD and MMUD only) or post transplantation cyclophosphamide, tacrolimus and MMF (haplo-donors only). 12 pts (15%) received ≥ 1 DLI preemptively past d+120 as planned. Results: Median overall survival (OS) and event-free survival (EFS) were 276 and 135 days (d). 33 pts (39%) had an OS >1y, and 22 (27%) an event free survival (EFS) >1y. 49 pts (59%) relapsed within the 1st y. Age at HSCT, type of AML (de novo vs secondary), remission status at time of HSCT, ratio of blasts in blood to bone marrow, donor type, type of RIC, mismatch and MRC risk classification had no significant impact on OS and EFS, whereas the number of treatment lines before HSCT significantly influenced OS (p=.05). Pts with ELN favorable/intermediate risk had longer EFS (p=.04, Figure 1A), but not OS (p=.12). On d+28 after HSCT, 43 pts (52%) had reached morphologic leukemia free state (MLFS), CR with incomplete count recovery (CRi) or CR, which was not associated with better OS or EFS (Figure 1B). In contrast, pts (n=49, 60%) with a donor chimerism (DC) ≥98% in BM had a significantly longer EFS (p<.01, Figure 1C) and OS (p<.01) than those with <98%. At d+100 32 pts (39%) were in MLFS, CRi or CR, and had a significant better for EFS (p<.01, Figure 1D) and OS (p<.05). Pts with a d+100 DC ≥98% in BM also had improved EFS (p=.02, Figure 1E) but not OS (p=.16). Acute Graft-versus-Host-Disease (GvHD) °II-IV occurred in 21 pts (26%). 13 pts (16%) developed any grade of chronic GvHD. Incidence of GvHD did not increase after DLI. Image:Summary/Conclusion: Despite the poor prognosis of r/r AML, a significant number of pts after FLAMSA RIC HSCT survived >1 y. Except ELN risk classification, there was no strong outcome predictor prior to HSCT. D+28 DC but not morphological remission in BM identifies pts at high risk for relapse after HSCT, allowing for additional post-HSCT strategies.